fig2

Figure 2. The abundance of HHV6 distinguishes (paternally inherited) fetal and maternal iciHHV6 and shows differing characteristic fragment size distributions. (A) Distributions of HHV6 abundance expressed as the number of viral HHV6 fragments divided over the total number of chromosomal fragments across all HHV6 positive samples on the x-asix. The y-axis represents a histogram (light blue bars) paired with kernel density estimation (dark blue line). Red dashed vertical lines indicate how samples are grouped into low (unintegrated/inherited HHV6; n = 479), intermediate (paternally inherited fetal iciHHV6; n = 226), and high (maternal iciHHV6; n = 441) abundance. (B) Scatter plots indicating the correlation between the calculated fetal fraction of a NIPT sample (y-axis) and the HHV6 abundance (x-axis). A significant correlation is only observed between the calculated fetal fraction and fetal iciHHV6 (red). (C) Different size distributions are observed for the three groups. Typical size distributions are observed with a peak of 143bp for fetal chromosomal cfDNA (red) and maternal cfDNA (blue). The presumed non-iciHHV6 fragments exhibit an increased frequency of short (50bp-100bp) cfDNA fragments. The dashed black line in all three figures indicates the typical 166bp fragment size of chromosomal cfDNA. HHV6: Human herpesvirus 6; iciHHV6: inherited chromosomally integrated HHV6 viruses; NIPT: non-invasive prenatal testing; cfDNA: cell-free DNA.